Abstract : Recently, a family of stimulatory ligands for the EGF/erbB family of receptor tyrosine kinases has been described. This family includes Neu differentiation factor (NDF), heregulin (HRG), acetylcholine receptor inducing activity (ARIA), and the glial growth factors (GGFs). This family of ligands, known collectively as the neuregulins, is comprised of alternatively spliced isoforms of a common gene. Interaction of the products of this gene with heterodimers and/or homodimers of the erbB receptors leads to their auto and transphosphorylation and subsequent interaction with SH-2 proteins including phospholipase C-y (PLC-y), the p85 subunit of posphotidylinositol 3'-kinase (PI-3 K), and the GTFase activating protein of ras (ras-GAP).